Disseminated intravascular coagulation (DIC) is a syndrome with an extremely high mortality rate, characterized by a tendency for bleeding due to consumption coagulopathy, and organ failure due to microvascular thrombosis, and rapid diagnosis and early treatment are necessary to maintain the life of patients and improve the prognosis. Conventional diagnosis of DIC in clinical practice includes the Japanese Ministry of Health and Welfare DIC diagnostic criteria, the measurements of various coagulation and fibrinolysis molecular markers [for example, soluble fibrin monomer (SF), D-dimer (DD), thrombin-antithrombin III complex (TAT), and α2-plasmin inhibitor/plasmin complex (PIC)], and the like. In addition, the International Society on Thrombosis and Haemostasis (ISTH) overt-DIC diagnostic criteria as a modification of the Japanese Ministry of Health and Welfare DIC diagnostic criteria, and the diagnostic criteria for the Japanese Association for Acute Medicine (JAAM) DIC are known. However, it is known that the Japanese Ministry of Health and Welfare DIC diagnostic criteria, and the ISTH overt-DIC diagnostic criteria exhibit low sensitivity, and the diagnostic criteria for JAAM DIC exhibits low specificity. Therefore, a study for diagnosis with high accuracy has been carried out (Non-patent literature 1) and, for example, the discovery of a marker with high sensitivity and high specificity is desired.
DIC is complicated with serious underlying diseases, such as malignant tumors, leukemia, or severe infections (or severe sepsis), and in particular, about 35% of patients suffering from severe sepsis are complicated with DIC. Since the mortality rate of patients complicated with DIC is increased from 22.2-26.5% to 40-46.2% in comparison with that of non-DIC, the diagnosis of septic DIC is very important to improve the prognosis of sepsis.
Because an underlying disease always exists in a DIC patient, the treatment for the underlying disease is first carried out. For example, chemotherapy for acute leukemia or advanced cancer, an antibiotic treatment sensitive to sepsis, or the like, is carried out. Because the underlying disease is diverse, it is important to grasp the patient's condition in order to select the most effective treatment. Even if a patient is diagnosed with DIC, it is needless to say that a wrong treatment would result in a serious condition. With respect to septic DIC, it was reported that patients resistant to a treatment based on an antithrombin preparation could be effectively treated using a recombinant thrombomodulin preparation with an anti-inflammatory effect, in addition to an anticoagulant effect (Non-patent literature 2).
Conventionally, septic DIC is diagnosed by the judgment of a doctor, on the basis of the diagnostic criteria for sepsis or DIC. For example, as described above, for the diagnosis of DIC, in addition to the Japanese Ministry of Health and Welfare DIC diagnostic criteria, various coagulation and fibrinolysis molecular markers [for example, soluble fibrin monomer (SF), D-dimer (DD), thrombin-antithrombin III complex (TAT), and α2-plasmin inhibitor/plasmin complex (PIC)] are measured in clinical practice. In addition, the ISTH overt-DIC diagnostic criteria as a modification of the Japanese Ministry of Health and Welfare DIC diagnostic criteria, and the diagnostic criteria for JAAM DIC are known. However, it is known that the Japanese Ministry of Health and Welfare DIC diagnostic criteria, and the ISTH overt-DIC diagnostic criteria exhibit low sensitivity, and the diagnostic criteria for JAAM DIC exhibit low specificity.
On the other hand, for the diagnosis of sepsis, blood culture, white blood cell count, body temperature, diagnostic imaging, the duration of systemic inflammatory response syndrome (SIRS), blood biochemical findings, and the like, are used as an index. Further, procalcitonin (PCT) and sCD14-ST were reported as markers capable of conveniently detecting sepsis.
It is disclosed that the sCD14-ST value in a sample collected from a sepsis patient is much higher than that of healthy persons, and sepsis is diagnosed by measuring sCD14-ST (Non-patent literature 3 and Patent literature 1). It is disclosed that sCD14-ST is measured using an antibody specific to sCD14-ST (Patent literature 1 and Patent literature 2). A method of rapidly detecting sCD14-ST and a method of evaluating the severity thereof are disclosed (Patent literature 2 and Non-patent literatures 3-5). As described above, it is known that sCD14-ST can be used to accurately diagnose sepsis accompanied by bacterial infection, but it has not been reported that sCD14-ST is useful in the detection of DIC.
As described above, a marker capable of conveniently and accurately diagnosing septic DIC (or infectious DIC) has not been reported, and the fact is that doctors are struggling to diagnose septic DIC (or infectious DIC), and the discovery of such a marker is desired.